In the treatment of patients it would often be desirable to monitor a given parameter indicating the actual state of the treatment, e.g. monitoring the concentration of a drug dispensed to the patient or a body substance influenced by the drug. A given monitor system for measuring the concentration of a given substance may be based on invasive or non-invasive measuring principles. An example of the latter would be a non-invasive glucose monitor arranged on the skin surface of a patient and using near-IR spectroscopy, however, the present invention is concerned with the introduction of a transcutaneous device such as a sensor element.
In recent years, a variety of electrochemical sensors have been developed for a range of applications, including medical applications for detecting and/or quantifying specific agents in a patient's blood. As one example, glucose sensors have been developed for use in obtaining an indication of blood glucose levels in a diabetic patient. Such readings can be especially useful in monitoring and/or adjusting a treatment regimen which typically includes regular administration of insulin to the patient. In this regard, blood glucose readings are particularly useful in conjunction with feedback controlled medication infusion devices, e.g. of the external type carried by the patient.
Glucose sensors (as well as the infusion devices) may be fully implanted or may comprise a subcutaneous sensor communicating with a component carried externally by the patient. In either case, the body responds to the implant as an insult and produces a specialized biochemical and cellular response which may lead to the development of a foreign body capsule around the implant and consequently may reduce the flux of glucose to the sensor. The percutaneous approach aims to acquire data during the first few days of this tissue response.
The monitoring method can be of three types: non-reactive, reversibly reactive or irreversibly reactive. The type of sensor which, thus far, has been found to function most effectively in vivo is the amperometric sensor relying on irreversible, transport-dependent reactive glucose assays. For a detailed review of the different types of glucose sensors reference is made to Adam Heller, Implanted electrochemical glucose sensors for the management of diabetes, Annu. Rev. Biomed. Eng. 1999, 01:153-175.
The sensor may be placed subcutaneously being connected to external equipment by wiring or the substance (fluid) to be analysed may be transported to an external sensor element, both arrangements requiring the placement of a subcutaneous component, the present invention addressing both arrangements. However, for simplicity the term “sensor” is used in the following for both types of sensor elements.
Turning to the sensor elements per se, relatively small and flexible electrochemical sensors have been developed for subcutaneous placement of sensor electrodes in direct contact with patient blood or other extra-cellular fluid (for example by MiniMed Inc., see U.S. Pat. No. 5,482,473), wherein such sensors can be used to obtain periodic or continuous readings over a period of time. In one form, flexible transcutaneous sensors are constructed in accordance with thin film mask techniques wherein an elongated sensor includes thin film conductive elements encased between flexible insulative layers of polyimide sheet or similar material. Such thin film sensors typically include exposed electrodes at a distal end for transcutaneous placement in direct contact with patient blood or other fluid, and exposed conductive contacts at an externally located proximal end for convenient electrical connection with a suitable monitor device.
Insertion devices for this type of sensors are described in, among others, U.S. Pat. Nos. 5,390,671, 5,391,950, 5,568,806 and 5,954,643.
More specifically, U.S. Pat. No. 5,954,643 discloses an insertion set comprising a mounting base defining an upwardly open channel for receiving and supporting a proximal end of a flexible thin film sensor, the sensor further including a distal segment with sensor electrodes thereon which protrudes from the mounting base for transcutaneous placement, wherein the sensor distal segment is slidably carried by a slotted insertion needle fitted through the assembled base. Placement of the insertion set against the patient's skin causes the insertion needle to pierce the skin to carry the sensor electrodes to the desired subcutaneous site, after which the insertion needle can be slidably withdrawn from the insertion set. The mounting base further includes a fitting and related snap latch members for mated slide-fit releasable coupling of conductive contact pads on a proximal end of the sensor to a cable connector for transmitting sensor signals to a suitable monitoring device.
A similar arrangement is known from U.S. Pat. No. 5,568,806 disclosing an insertion set comprising an insertion needle extending through a mounting base adapted for mounting onto the patient's skin. A flexible thin film sensor includes a proximal segment carried by the mounting base and adapted for electrical connection to a suitable monitor or the like, and a distal segment protruding from the mounting base with sensor electrodes thereon for transcutaneous placement. The distal segment of the sensor and a distal segment of the insertion needle are positioned within a flexible cannula which extends from the mounting base, whereby placement of the mounting base onto the patient's skin causes the insertion needle to pierce the skin for transcutaneous placement of the cannula with the sensor therein. The insertion needle can then be withdrawn from the cannula and the mounting base to leave the sensor distal segment at the selected insertion position, with the sensor electrodes being exposed to patient blood or other extra cellular fluid via a window formed in the cannula.
Although the above-described insertion sets provide reliable means for introducing a needle formed sensor (i.e. having an oblong, needle-like appearance but not necessarily comprising a pointed distal tip), a number of disadvantages still prevail.
As stated above, the percutaneous approach aims to acquire data during the first few days after insertion of the device, after which a new sensor is placed at a different place. Although such a short period of time will remove the problems of long-term encapsulating reactions, a tissue response will immediately begin after insertion, the body trying to isolate the implanted object by tissue remodelling. This response may have a profound and varying effect on glucose transport, even over a short period of use, e.g. 3-4 days, this calling for recalibration of the implanted sensor.
Besides the technical aspects of recalibration, opinions differ about how often recalibration will be necessary to ensure reliable performance and what patients may be willing to accept. Based on current experience with subcutaneous sensors, it is believed that the needle-type sensors will have to be recalibrated to blood glucose values obtained from the traditional fingerstick method at least once a day and maybe more often. In addition, putting calibration in the hands of patients presents safety and quality issues.
Although the available needle-type sensors are relatively small, they are still much larger than the infusion needles normally used when administering, for example, insulin. A further problem is therefore the pain and discomfort associated with the introduction of a needle sensor, for example when using the above-described prior art devices.